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The sweet taste preference of humans is an important adaptation to ensure the acquisition of carbohydrate nutrition; however, overconsumption of sweet foods can potentially lead to diseases such as obesity and diabetes. Although previous studies have suggested that interindividual variation of human sweet taste preference is heritable, genetic loci associated with the trait have yet to be fully elucidated. Here, we genotyped 12,312 Japanese participants using the HumanCore-12+ Custom BeadChip or the HumanCore-24 Custom BeadChip microarrays. The sweet taste preference of the participants was surveyed via an internet-based questionnaire, resulting in a five-point scale of sweet taste preference. The genome-wide meta-analysis of the Japanese participants revealed a strong association between the 12q24 locus and sweet taste preference scale (P = 2.8 × 10−70). The lead variant rs671 is monoallelic in non-East Asian populations and is located in the aldehyde dehydrogenase (ALDH2) gene, encoding an enzyme involved in alcohol metabolism. The association between the minor allele of rs671 and sweet taste preference was attenuated by adjusting for alcohol drinking. The subgroup analysis showed that the effect of rs671 on sweet taste preference was greater in males than in females. In conclusion, we found an association between the 12q24 locus and sweet taste preference in the Japanese population, and showed that the adjustment for drinking habits attenuated the association. This novel genetic association may provide new clues to elucidate mechanisms determining sweet taste preferences.

Background Tooth loss significantly impacts oral function and overall health deterioration. Dental caries and periodontal disease are major contributors to tooth loss, emphasizing the critical need to prevent these conditions. Genetic studies have played a crucial role in deepening our understanding of the underlying mechanisms of these diseases. While large-scale genome-wide association studies (GWAS) on dental caries and periodontal disease have been conducted extensively, research focusing on Asian populations remains limited. Given substantial genetic and lifestyle variations across ethnicities, conducting studies across diverse populations is imperative. This study aimed to uncover new insights into the genetic mechanisms of these diseases, contributing to broader knowledge and potential targeted interventions. Methods We conducted a GWAS using genome data from 45,525 Japanese individuals, assessing their self-reported history of dental caries and periodontal disease. Additionally, we performed a meta-analysis by integrating our results with those from a previous large-scale GWAS predominantly involving European populations. Results While no new loci associated with periodontal disease were identified, we discovered two novel loci associated with dental caries. The lead variants of these loci were intron variant rs10974056 in GLIS3 and intron variant rs4801882 in SIGLEC5 . Conclusion Our study findings are anticipated to advance understanding of the underlying mechanisms of dental caries and periodontal disease. Thes insights may inform better management strategies for patients affected by these conditions.

Sarcopenia is the decline in skeletal muscle mass, strength, and functions, which decreases the quality of life in elderly people. This study investigated the suppressive effect of turmeric (Curcuma longa) extract (TE) on muscle atrophy in dexamethasone (DEX)-treated mice and C2C12 myotubes. DEX treatment significantly decreased the muscle weight and significantly increased Fbxo32 and Murf1 expression in mice, and these changes were suppressed by the supplementation of an AIN-93 based diet with 2% TE. A similar pattern was observed in FBXO32 and MuRF1 protein expression. In C2C12 myotubes, DEX treatment significantly increased FBXO32 and MuRF1 gene and protein expression, and these increases were significantly suppressed by TE supplementation at a concentration of 200 µg/mL. Furthermore, one of the five TE fractions, which were separated by high-performance liquid chromatography had a similar effect with TE supplementation. The present study proposes the suppressive effect of turmeric on sarcopenia.

Skeletal muscle is programmable, and early-life nutritional stimuli may form epigenetic memory in the skeletal muscle, thus impacting adult muscle function, aging, and longevity. In the present study, we designed a one-month protein restriction model using post-weaning rats, followed by a two-month rebound feeding, to investigate how early-life protein restriction affects overall body growth and muscle development and whether these influences could be corrected by rebound feeding. We observed comprehensive alterations immediately after protein restriction, including retarded growth, altered biochemical indices, and disturbed hormone secretion. Transcriptome profiling of the gastrocnemius muscle followed by gene ontology analyses revealed that “myogenic differentiation functions” were upregulated, while “protein catabolism” was downregulated as a compensatory mechanism, with enhanced endoplasmic reticulum stress and undesired apoptosis. Furthermore, methylome profiling of the gastrocnemius muscle showed that protein restriction altered the methylation of apoptotic and hormone secretion-related genes. Although most of the alterations were reversed after rebound feeding, 17 genes, most of which play roles during muscle development, remained altered at the transcriptional level. In summary, early-life protein restriction may undermine muscle function in the long term and affect skeletal muscle development at the both transcriptional and methylation levels, which may hazard future muscle health.

Niemann-Pick C1-Like 1 (NPC1L1) mediates cholesterol absorption, and ezetimibe is a potent NPC1L1 inhibitor applicable for medication of hypercholesterolemia. Epidemiological studies demonstrated that consumption of polyphenols correlates with a decreased risk for atherosclerosis due to their antioxidant effect. This activity can hardly be attributable to the antioxidant activity only, and we hypothesized that polyphenols inhibit intestinal transport of cholesterol. We elucidated the kinetic parameters of intestinal cholesterol absorption, screened several polyphenols for their ability to specifically inhibit intestinal cholesterol absorption, and determined the inhibitory effects of selected flavonoids in vitro and in vivo. The concentration-dependent uptake of cholesterol by Caco-2 cells obeyed a monophasic saturation process. This indicates the involvement of an active-passive transport, i.e., NPC1L1. Parameters of cholesterol uptake by Caco-2 cells were as follows: Jmax, Kt, and Kd were 6.89±2.96 19.03±11.58 µM, and 0.11±0.02 pmol/min/mg protein, respectively. Luteolin and quercetin inhibited cholesterol absorption by Caco-2 cells and human embryonic kidney 293T cells expressing NPC1L1. When preincubated Caco-2 cells with luteolin and quercetin before the assay, cholesterol uptake significantly decreased. The inhibitory effects of these flavonoids were maintained for up to 120 min. The level of inhibition and irreversible effects were similar to that of ezetimibe. Serum cholesterol levels significantly decreased more in rats fed both cholesterol and luteolin (or quercetin), than in those observed in the cholesterol feeding group. As quercetin induced a significant decrease in the levels of NPC1L1 mRNA in Caco-2 cells, the in vivo inhibitory effect may be due to the expression of NPC1L1. These results suggest that luteolin and quercetin reduce high blood cholesterol levels by specifically inhibiting intestinal cholesterol absorption mediated by NPC1L1.

Chronological aging is commonly accompanied by chronic low-grade inflammation (or “inflammaging”), a contributor to the development of age-related chronic diseases. Aging increases oxidative stress that accelerates telomere shortening, leading to cell senescence and the generation of senescence-associated secretory phenotype (SASP) that exacerbates inflammation. Dietary antioxidants may help protect telomeres and attenuate inflammation. Thyme essential oil (TEO), reported for its potency against neuroinflammation, was fed to chronologically aged C57BL/6J mice for 24 weeks. The TEO diet showed notable impacts on the hippocampus, indicated by lower expression of the aging-related gene p16INK4A (p = 0.0783) and significantly lower expression of cyclin D kinase Cdk4 and Cdk6 (p < 0.05) compared to the age-matched control mice. The TEO group also showed significantly lower gene expression of the pro-inflammatory cytokine Il6 (p < 0.05) in the hippocampus and lower Il1b expression in the liver and cerebellum (p < 0.05). In vitro experiments conducted on NIH-3T3 cells expressing SASP revealed the dose-dependent anti-inflammatory activity of TEO. Remarkably, TEO diet-fed mice showed higher survival rates and significantly longer blood telomere lengths than the control mice. Monoterpene antioxidants in TEO, particularly thymol and p-cymene, may primarily contribute to the anti-inflammatory and telomere-protecting activities of TEO.

Muscle atrophy is one of the main causes of sarcopenia—the age-related loss of skeletal muscle. In this study, we investigated the effect of turmeric (Curcuma longa) extract (TE) supplementation on age-related muscle atrophy in a senescence-accelerated mouse model and explored the underlying mechanisms. Twenty-six-week-old male, senescence-accelerated mouse resistant (SAMR) mice received the AIN-93G basal diet, while twenty-six-week-old male, senescence-accelerated mouse prone 8 (SAMP8) mice received the AIN-93G basal diet or a 2% TE powder-supplemented diet for ten weeks. Our findings revealed that TE supplementation showed certain effects on ameliorating the decrease in body weight, tibialis anterior weight, and mesenteric fat tissue weight in SAMP8 mice. TE improved gene expression in the glucocorticoid receptor-FoxO signaling pathway in skeletal muscle, including redd1, klf15, foxo1, murf1, and mafbx. Furthermore, TE might have the certain potential on improving the dynamic balance between anabolic and catabolic processes by inhibiting the binding of glucocorticoid receptor or FoxO1 to the glucocorticoid response element or FoxO-binding element in the MuRF1 promoter in skeletal muscle, thereby promoting muscle mass and strength, and preventing muscle atrophy and sarcopenia prevention. Moreover, TE may have reduced mitochondrial damage and maintained cell growth and division by downregulating the mRNA expression of the genes mfn2 and tsc2. Thus, the results indicated TE’s potential for preventing age-related muscle atrophy and sarcopenia.

Prevention of muscle atrophy contributes to improved quality of life and life expectancy. In this study, we investigated the effects of laurel, selected from 34 spices and herbs, on dexamethasone (DEX)-induced skeletal muscle atrophy and deciphered the underlying mechanisms. Co-treatment of C2C12 myotubes with laurel for 12 h inhibited the DEX-induced expression of intracellular ubiquitin ligases—muscle atrophy F-box (atrogin-1/MAFbx) and muscle RING finger 1 (MuRF1)—and reduction in myotube diameter. Male Wistar rats were supplemented with 2% laurel for 17 days, with DEX-induced skeletal muscle atrophy occurring in the last 3 days. Laurel supplementation inhibited the mRNA expression of MuRF1, regulated DNA damage and development 1 (Redd1), and forkhead box class O 1 (Foxo1) in the muscles of rats. Mechanistically, we evaluated the effects of laurel on the cellular proteolysis machinery—namely, the ubiquitin/proteasome system and autophagy—and the mTOR signaling pathway, which regulates protein synthesis. These data indicated that the amelioration of DEX-induced skeletal muscle atrophy induced by laurel, is mainly mediated by the transcriptional inhibition of downstream factors of the ubiquitin-proteasome system. Thus, laurel may be a potential food ingredient that prevents muscle atrophy.

Many studies have shown the beneficial effects of calorie restriction (CR) on rodents’ aging; however, the molecular mechanism explaining these beneficial effects is still not fully understood. Previously, we conducted transcriptomic analysis on rat liver with short-term and mild-to-moderate CR to elucidate its early response to such diet. Here, we expanded transcriptome analysis to muscle, adipose tissue, intestine, and brain and compared the gene expression profiles of these multiple organs and of our previous dataset. Several altered gene expressions were found, some of which known to be related to CR. Notably, the commonly regulated genes by CR include nicotinamide phosphoribosyltransferase and heat shock protein 90, which are involved in declining the aging process and thus potential therapeutic targets for aging-related diseases. The data obtained here provide information on early response markers and key mediators of the CR-induced delay in aging as well as on age-associated pathological changes in mammals.

Diet-induced obesity is often associated with gut microbiota dysbiosis, lipid metabolism disorders, and chronic inflammation. Consumption of the pseudocereal Amaranthus mangostanus has multiple nutritional benefits. We investigated the effects of dietary amaranth on lipid metabolism and gut microbiota in high-fat (HF) diet-fed mice. C57BL/6J mice were provided either a control diet, HF diet, or HF diet containing 10% amaranth powder (Ama) for 8 weeks. Ama supplementation significantly reduced the levels of triglycerides, total cholesterol, and phospholipids in the liver. Moreover, Ama supplementation downregulated the expression of lipogenesis-related genes including Hmgcr, Fdt1, and Sgle in the liver. The gut microbiota analysis showed that Ama supplementation reversed HF diet-induced reduction in bacterial diversity and richness. Additionally, beta diversity analysis of the inter-group variability in community structure showed a clear separation between the HF and Ama groups. Linear discriminant analysis effect size analysis revealed that 11 taxa were enriched in the Ama group, whereas 9 taxa were increased in the HF group. We found that family Porphyromonadaceae and unclassified S24-7 showed a strong positive and negative correlation with the lipid parameters, respectively. Taken together, these results indicated that dietary Ama may attenuate HF diet-induced deterioration of gut microbiota structure and hepatic lipid metabolism.